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Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis 暴露于全氟辛烷磺酸(PFAS)化学品会诱发肝脏脂肪变性中脂质代谢关键限速步骤的性别改变
Frontiers in toxicology Pub Date : 2024-06-05 DOI: 10.3389/ftox.2024.1390196
Archana Hari, M. AbdulHameed, Michele R Balik-Meisner, D. Mav, Dhiral P. Phadke, Elizabeth H. Scholl, Ruchir R. Shah, Warren Casey, Scott S. Auerbach, Anders Wallqvist, Venkat R. Pannala
{"title":"Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis","authors":"Archana Hari, M. AbdulHameed, Michele R Balik-Meisner, D. Mav, Dhiral P. Phadke, Elizabeth H. Scholl, Ruchir R. Shah, Warren Casey, Scott S. Auerbach, Anders Wallqvist, Venkat R. Pannala","doi":"10.3389/ftox.2024.1390196","DOIUrl":"https://doi.org/10.3389/ftox.2024.1390196","url":null,"abstract":"Toxicants with the potential to bioaccumulate in humans and animals have long been a cause for concern, particularly due to their association with multiple diseases and organ injuries. Per- and polyfluoro alkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) are two such classes of chemicals that bioaccumulate and have been associated with steatosis in the liver. Although PFAS and PAH are classified as chemicals of concern, their molecular mechanisms of toxicity remain to be explored in detail. In this study, we aimed to identify potential mechanisms by which an acute exposure to PFAS and PAH chemicals can induce lipid accumulation and whether the responses depend on chemical class, dose, and sex. To this end, we analyzed mechanisms beginning with the binding of the chemical to a molecular initiating event (MIE) and the consequent transcriptomic alterations. We collated potential MIEs using predictions from our previously developed ToxProfiler tool and from published steatosis adverse outcome pathways. Most of the MIEs are transcription factors, and we collected their target genes by mining the TRRUST database. To analyze the effects of PFAS and PAH on the steatosis mechanisms, we performed a computational MIE-target gene analysis on high-throughput transcriptomic measurements of liver tissue from male and female rats exposed to either a PFAS or PAH. The results showed peroxisome proliferator-activated receptor (PPAR)-α targets to be the most dysregulated, with most of the genes being upregulated. Furthermore, PFAS exposure disrupted several lipid metabolism genes, including upregulation of fatty acid oxidation genes (Acadm, Acox1, Cpt2, Cyp4a1-3) and downregulation of lipid transport genes (Apoa1, Apoa5, Pltp). We also identified multiple genes with sex-specific behavior. Notably, the rate-limiting genes of gluconeogenesis (Pck1) and bile acid synthesis (Cyp7a1) were specifically downregulated in male rats compared to female rats, while the rate-limiting gene of lipid synthesis (Scd) showed a PFAS-specific upregulation. The results suggest that the PPAR signaling pathway plays a major role in PFAS-induced lipid accumulation in rats. Together, these results show that PFAS exposure induces a sex-specific multi-factorial mechanism involving rate-limiting genes of gluconeogenesis and bile acid synthesis that could lead to activation of an adverse outcome pathway for steatosis.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141385281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does pyrethroid exposure lower human semen quality? a systematic review and meta-analysis. 系统回顾和荟萃分析:接触拟除虫菊酯是否会降低人类精液质量?
IF 3.6
Frontiers in toxicology Pub Date : 2024-05-30 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1395010
Roland Eghoghosoa Akhigbe, Precious Adeoye Oyedokun, Tunmise Maryanne Akhigbe, Suliat Adenike, Ayoola Abimbola Oladipo, Jennifer Rose Hughes
{"title":"Does pyrethroid exposure lower human semen quality? a systematic review and meta-analysis.","authors":"Roland Eghoghosoa Akhigbe, Precious Adeoye Oyedokun, Tunmise Maryanne Akhigbe, Suliat Adenike, Ayoola Abimbola Oladipo, Jennifer Rose Hughes","doi":"10.3389/ftox.2024.1395010","DOIUrl":"10.3389/ftox.2024.1395010","url":null,"abstract":"<p><p><b>Background:</b> Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. <b>Materials and methods:</b> The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). <b>Results:</b> Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. <b>Conclusion:</b> Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global challenges in aging: insights from comparative biology and one health. 全球老龄化的挑战:比较生物学和一体健康的启示。
Frontiers in toxicology Pub Date : 2024-05-30 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1381178
Mary Ann Ottinger, Jacquelyn K Grace, Terri J Maness
{"title":"Global challenges in aging: insights from comparative biology and one health.","authors":"Mary Ann Ottinger, Jacquelyn K Grace, Terri J Maness","doi":"10.3389/ftox.2024.1381178","DOIUrl":"10.3389/ftox.2024.1381178","url":null,"abstract":"<p><p>The well-being of wildlife populations, ecosystem health, and human health are interlinked, and preserving wildlife is crucial for sustaining healthy ecosystems. Wildlife numbers, and in particular avian populations, have steeply declined over the past century, associated with anthropogenic factors originating from industry, urbanization, changing land use, habitat loss, pollution, emerging diseases, and climate change. All these factors combine to exert increasing stress and impair health for both humans and wildlife, with diminished metabolic, immune, and reproductive function, deteriorating overall health, and reduced longevity. The \"toxic aging coin\" suggests that these stressors may have dual impacts on aging-they can accelerate the aging process, and older individuals may struggle to cope with pollutants compared to younger ones. These responses are reflected in the health and productivity of individuals, and at a larger scale, the health and ability of populations to withstand disturbances. To understand the potential risk to health over the lifespan, it is important to articulate some of these global challenges and consider both their impacts on aging populations and on the aging process. In this review, we use the toxic aging coin and One Health conceptual frameworks to examine the interconnected health of humans, wildlife, and ecosystems. This exploration aims to develop proactive approaches for optimizing wildlife and human health.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The DaNa projects: public communication of (nano)material safety data-from conspiracy theories to study quality. DaNa 项目:(纳米)材料安全数据的公开交流--从阴谋论到研究质量。
Frontiers in toxicology Pub Date : 2024-05-28 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1382458
Dana Kühnel, Harald F Krug, Christoph Steinbach, Katja Nau
{"title":"The DaNa projects: public communication of (nano)material safety data-from conspiracy theories to study quality.","authors":"Dana Kühnel, Harald F Krug, Christoph Steinbach, Katja Nau","doi":"10.3389/ftox.2024.1382458","DOIUrl":"10.3389/ftox.2024.1382458","url":null,"abstract":"<p><p>In this perspective, the authors give their view on the developments and experiences on communicating on (nano)materials safety. We would like to share our experiences with the scientific community in order to make them useful for future communication activities. We present the long-term work of the science communication projects DaNa, DaNa2.0 and DaNa4.0, running from 2009 to 2023. Starting in the early 2000s with the beginnings of nanotechnology research, communication on the safety of nanomaterials with the public was still very new and faced the projects with many challenges. Today, science communication is indispensable for the dissemination of scientific findings and a fact-based approach like the DaNa \"Knowledge Base Materials\" creates a trustworthy dialogue with the public. This long-term project series has made a significant contribution to communication on the safety of nanomaterials, perhaps even the largest among publicly funded project series worldwide.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ICH S1 prospective evaluation study and weight of evidence assessments: commentary from industry representatives ICH S1 前瞻性评估研究和证据权重评估:业界代表的评论意见
Frontiers in toxicology Pub Date : 2024-05-23 DOI: 10.3389/ftox.2024.1377990
John L. Vahle, Joe Dybowski, Michael Graziano, Shigeru Hisada, Jose Lebron, Thomas Nolte, Ronald Steigerwalt, Kenjiro Tsubota, Frank D. Sistare
{"title":"ICH S1 prospective evaluation study and weight of evidence assessments: commentary from industry representatives","authors":"John L. Vahle, Joe Dybowski, Michael Graziano, Shigeru Hisada, Jose Lebron, Thomas Nolte, Ronald Steigerwalt, Kenjiro Tsubota, Frank D. Sistare","doi":"10.3389/ftox.2024.1377990","DOIUrl":"https://doi.org/10.3389/ftox.2024.1377990","url":null,"abstract":"Industry representatives on the ICH S1B(R1) Expert Working Group (EWG) worked closely with colleagues from the Drug Regulatory Authorities to develop an addendum to the ICH S1B guideline on carcinogenicity studies that allows for a weight-of-evidence (WoE) carcinogenicity assessment in some cases, rather than conducting a 2-year rat carcinogenicity study. A subgroup of the EWG composed of regulators have published in this issue a detailed analysis of the Prospective Evaluation Study (PES) conducted under the auspices of the ICH S1B(R1) EWG. Based on the experience gained through the Prospective Evaluation Study (PES) process, industry members of the EWG have prepared the following commentary to aid sponsors in assessing the standard WoE factors, considering how novel investigative approaches may be used to support a WoE assessment, and preparing appropriate documentation of the WoE assessment for presentation to regulatory authorities. The commentary also reviews some of the implementation challenges sponsors must consider in developing a carcinogenicity assessment strategy. Finally, case examples drawn from previously marketed products are provided as a supplement to this commentary to provide additional examples of how WoE criteria may be applied. The information and opinions expressed in this commentary are aimed at increasing the quality of WoE assessments to ensure the successful implementation of this approach.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141104737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain. 二异丙基氟磷酸酯急性中毒会促进成年雄性大鼠脑细胞衰老
IF 3.6
Frontiers in toxicology Pub Date : 2024-04-30 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1360359
Yi-Hua Tsai, Eduardo A González, Ana C G Grodzki, Donald A Bruun, Naomi H Saito, Danielle J Harvey, Pamela J Lein
{"title":"Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.","authors":"Yi-Hua Tsai, Eduardo A González, Ana C G Grodzki, Donald A Bruun, Naomi H Saito, Danielle J Harvey, Pamela J Lein","doi":"10.3389/ftox.2024.1360359","DOIUrl":"10.3389/ftox.2024.1360359","url":null,"abstract":"<p><p>Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100β, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated β-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: Neglected tropical diseases: tackling the challenges of a global world. 社论:被忽视的热带疾病:应对全球挑战。
Frontiers in toxicology Pub Date : 2024-04-30 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1417438
Armanda Rodrigues, Gabriela Santos-Gomes
{"title":"Editorial: Neglected tropical diseases: tackling the challenges of a global world.","authors":"Armanda Rodrigues, Gabriela Santos-Gomes","doi":"10.3389/ftox.2024.1417438","DOIUrl":"10.3389/ftox.2024.1417438","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of a varied set of stimuli on a suite of immunological parameters within peripheral blood mononuclear cells: toward a non-animal approach for assessing immune modulation by materials intended for human use. 各种刺激对外周血单核细胞内一系列免疫学参数的影响:采用非动物方法评估供人类使用的材料对免疫的调节作用。
Frontiers in toxicology Pub Date : 2024-04-26 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1335110
Stella Cochrane, Ramya Rajagopal, David Sheffield, Fay Stewart, Lindsay Hathaway, Nicholas M Barnes, Omar Qureshi, John Gordon
{"title":"Impact of a varied set of stimuli on a suite of immunological parameters within peripheral blood mononuclear cells: toward a non-animal approach for assessing immune modulation by materials intended for human use.","authors":"Stella Cochrane, Ramya Rajagopal, David Sheffield, Fay Stewart, Lindsay Hathaway, Nicholas M Barnes, Omar Qureshi, John Gordon","doi":"10.3389/ftox.2024.1335110","DOIUrl":"10.3389/ftox.2024.1335110","url":null,"abstract":"<p><p><b>Introduction:</b> In toxicology, steps are being taken towards more mechanism-focused and human relevant approaches to risk assessment, requiring new approaches and methods. Additionally, there is increasing emphasis by regulators on risk assessment of immunotoxicity. <b>Methods:</b> Here we present data from a peripheral blood mononuclear cell (PBMC) system whereby a varied set of stimuli, including those against the TCR and Toll-like receptors, enable readouts of cytokine and prostaglandin E2 (PGE2) production with monocyte, T cell and B cell viability, proliferation, and associated activation markers. In addition to results on the impact of the stimuli used, initial profiling data for a case study chemical, curcumin, is presented, illustrating how the system can be used to generate information on the impact of exogenous materials on three major constituent immune cell subsets for use in risk assessment and to direct follow-on studies. <b>Results:</b> The different stimuli drove distinct responses, not only in relation to the \"quantity\" of the response but also the \"quality\". Curcumin had a limited impact on the B cell parameters measured, with the stimuli used, and it was noted that in contrast to T cells where there was either no impact or a reduction in viability and proliferation with increasing concentration, for B cells there was a small but significant increase in both measurements at curcumin concentrations below 20 µM. Similarly, whilst expression of activation markers by T cells was reduced by the highest concentration of curcumin, they were increased in B cells. Curcumin only impacted the viability of stimulated monocytes at the highest concentration and had differential impact on different activation markers. Levels of all cytokines and PGE2 were reduced at higher concentrations. <b>Discussion:</b> Although the platform has certain limitations, it nevertheless enables assessment of healthy baseline monocyte, T-, and B-cell responses, and scrutiny of the impact of different stimuli to detect potential immune suppression or enhancement from exogenous materials. In the case of curcumin, a pattern of responses indicative of immune suppressive / anti-inflammatory effects was detected. It is an accessible, highly modifiable system that can be used to screen materials and guide further studies, providing a holistic, integrated picture of effects.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project. 用于评估发育期和成年期神经毒性的监管新方法:PARC 第 5 工作包项目。
Frontiers in toxicology Pub Date : 2024-04-26 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1359507
Tamara Tal, Oddvar Myhre, Ellen Fritsche, Joëlle Rüegg, Kai Craenen, Kiara Aiello-Holden, Caroline Agrillo, Patrick J Babin, Beate I Escher, Hubert Dirven, Kati Hellsten, Kristine Dolva, Ellen Hessel, Harm J Heusinkveld, Yavor Hadzhiev, Selma Hurem, Karolina Jagiello, Beata Judzinska, Nils Klüver, Anja Knoll-Gellida, Britta A Kühne, Marcel Leist, Malene Lislien, Jan L Lyche, Ferenc Müller, John K Colbourne, Winfried Neuhaus, Giorgia Pallocca, Bettina Seeger, Ilka Scharkin, Stefan Scholz, Ola Spjuth, Monica Torres-Ruiz, Kristina Bartmann
{"title":"New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project.","authors":"Tamara Tal, Oddvar Myhre, Ellen Fritsche, Joëlle Rüegg, Kai Craenen, Kiara Aiello-Holden, Caroline Agrillo, Patrick J Babin, Beate I Escher, Hubert Dirven, Kati Hellsten, Kristine Dolva, Ellen Hessel, Harm J Heusinkveld, Yavor Hadzhiev, Selma Hurem, Karolina Jagiello, Beata Judzinska, Nils Klüver, Anja Knoll-Gellida, Britta A Kühne, Marcel Leist, Malene Lislien, Jan L Lyche, Ferenc Müller, John K Colbourne, Winfried Neuhaus, Giorgia Pallocca, Bettina Seeger, Ilka Scharkin, Stefan Scholz, Ola Spjuth, Monica Torres-Ruiz, Kristina Bartmann","doi":"10.3389/ftox.2024.1359507","DOIUrl":"10.3389/ftox.2024.1359507","url":null,"abstract":"<p><p>In the European regulatory context, rodent <i>in vivo</i> studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with <i>in vitro</i> or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific <i>in vivo</i> studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project. 更正:为内分泌代谢干扰物的鉴定和特征描述开发新的方法--PARC 项目。
Frontiers in toxicology Pub Date : 2024-03-25 eCollection Date: 2024-01-01 DOI: 10.3389/ftox.2024.1394396
Albert Braeuning, Patrick Balaguer, William Bourguet, Jordi Carreras-Puigvert, Katreece Feiertag, Jorke H Kamstra, Dries Knapen, Dajana Lichtenstein, Philip Marx-Stoelting, Jonne Rietdijk, Kristin Schubert, Ola Spjuth, Evelyn Stinckens, Kathrin Thedieck, Rik van den Boom, Lucia Vergauwen, Martin von Bergen, Neele Wewer, Daniel Zalko
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